Eun Yeon Joo

STUDY OBJECTIVE: To investigate the structural changes in patients with chronic primary insomnia and the relationships with clinical features of insomnia. DESIGN: Statistical parametric mapping 8-based voxel-based morphometry was used to identify differences in regional gray and white matter between patients with chronic primary insomnia and normal controls. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Twenty-seven patients and 27 age/sex-matched controls. INTERVENTIONS: -tests with age, sex, and intracranial volume as covariates. MEASUREMENTS AND RESULTS: The patients were a mean age of 52.3 y and had a mean history of insomnia of 7.6 y. Patients displayed cognitive deficits in attention, frontal/executive function, and nonverbal memory. Patients also displayed significantly reduced gray matter concentrations (GMCs) in dorsolateral prefrontal and pericentral cortices, superior temporal gyrus, and cerebellum and decreased gray matter volumes in medial frontal and middle temporal gyri compared with control patients with the cluster threshold ≥ 50 voxels at the level of uncorrected P < 0.001. Negative correlations were found between GMC of the prefrontal cortex and insomnia severity and the wakefulness after sleep onset, and between GMC of pericentral cortex and sleep latencies. None of the findings continued to be significant after correction for multiple comparisons. CONCLUSIONS: We found gray matter deficits in multiple brain regions including bilateral frontal lobes in patients with psychophysiologic insomnia. Gray matter deficit of the pericentral and lateral temporal areas may be associated with the difficulties in sleep initiation and maintenance. It is still unclear whether gray matter reductions are a preexisting abnormality or a consequence of insomnia. CITATION: 2013;36(7):999-1007.

STUDY OBJECTIVES: To investigate differences in brain gray matter concentrations or volumes in patients with obstructive sleep apnea syndrome (OSA) and healthy volunteers. DESIGNS: Optimized voxel-based morphometry, an automated processing technique for MRI, was used to characterize structural differences in gray matter in newly diagnosed male patients. SETTING: University hospital. PATIENTS AND PARTICIPANTS: The study consisted of 36 male OSA and 31 non-apneic male healthy volunteers matched for age (mean age, 44.8 years). INTERVENTIONS: Using the t-test, gray matter differences were identified. The statistical significance level was set to a false discovery rate P < 0.05 with an extent threshold of k(E) > 200 voxels. MEASUREMENTS AND RESULTS: The mean apnea-hypopnea index (AHI) of patients was 52.5/h. On visual inspection of MRI, no structural abnormalities were observed. Compared to healthy volunteers, the gray matter concentrations of OSA patients were significantly decreased in the left gyrus rectus, bilateral superior frontal gyri, left precentral gyrus, bilateral frontomarginal gyri, bilateral anterior cingulate gyri, right insular gyrus, bilateral caudate nuclei, bilateral thalami, bilateral amygdalo-hippocampi, bilateral inferior temporal gyri, and bilateral quadrangular and biventer lobules in the cerebellum (false discovery rate P < 0.05). Gray matter volume was not different between OSA patients and healthy volunteers. CONCLUSIONS: The brain gray matter deficits may suggest that memory impairment, affective and cardiovascular disturbances, executive dysfunctions, and dysregulation of autonomic and respiratory control frequently found in OSA patients might be related to morphological differences in the brain gray matter areas.

STUDY OBJECTIVES: Despite compelling evidence from animal studies indicating hippocampal subfield-specific vulnerability to poor sleep quality and related cognitive impairment, there have been no human magnetic resonance imaging (MRI) studies investigating the relationship between hippocampal subfield volume and sleep disturbance. Our aim was to investigate the pattern of volume changes across hippocampal subfields in patients with primary insomnia relative to controls. DESIGN: Pointwise morphometry allowed for volume measurements of hippocampal regions on T1-weighted MRI. SETTING: University hospital. PATIENTS: Twenty-seven unmedicated patients (age: 51.2 ± 9.6 y) and 30 good sleepers as controls (50.4 ± 7.1 y). INTERVENTIONS: N/A. MEASUREMENTS: We compared hippocampal subfield volumes between patients and controls and correlated volume with clinical and neuropsychological features in patients. RESULTS: Patients exhibited bilateral atrophy across all hippocampal subfields (P < 0.05 corrected). Cornu ammonis (CA) 1 subfield atrophy was associated with worse sleep quality (higher Pittsburgh Sleep Quality Index and higher arousal index of polysomnography) (r < -0.45, P < 0.005). The volume of the combined region, including the dentate gyrus (DG) and CA3-4, negatively correlated with verbal memory, verbal information processing, and verbal fluency in patients (|r| > 0.45, P < 0.05). Hemispheric volume asymmetry of this region (left smaller than right) was associated with impaired verbal domain functions (r = 0.50, P < 0.005). CONCLUSION: Hippocampal subfield atrophy in chronic insomnia suggests reduced neurogenesis in the dentate gyrus (DG) and neuronal loss in the cornu ammonis (CA) subfields in conditions of sleep fragmentation and related chronic stress condition. Atrophy in the CA3-4-DG region was associated with impaired cognitive functions in patients. These observations may provide insight into pathophysiological mechanisms that make patients with chronic sleep disturbance vulnerable to cognitive impairment. CITATION: Joo EY, Kim H, Suh S, Hong SB. Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.

Obesity is a common disorder with many complications. Although chronodisruption plays a role in obesity, few epidemiological studies have investigated the association between artificial light at night (ALAN) and obesity. Since sleep health is related to both obesity and ALAN, we investigated the association between outdoor ALAN and obesity after adjusting for sleep health. We also investigated the association between outdoor ALAN and sleep health. This cross-sectional survey included 8526 adults, 39-70 years of age, who participated in the Korean Genome and Epidemiology Study. Outdoor ALAN data were obtained from satellite images provided by the US Defense Meteorological Satellite Program. We obtained individual data regarding outdoor ALAN; body mass index; depression; and sleep health including sleep duration, mid-sleep time, and insomnia; and other demographic data including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking status and consumption of caffeine or alcohol before sleep. A logistic regression model was used to investigate the association between outdoor ALAN and obesity. The prevalence of obesity differed significantly according to sex (women 47% versus men 39%, p < 0.001) and outdoor ALAN (high 55% versus low 40%, p < 0.001). Univariate logistic regression analysis revealed a significant association between high outdoor ALAN and obesity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.14-1.35, p < 0.001). Furthermore, multivariate logistic regression analyses showed that high outdoor ALAN was significantly associated with obesity after adjusting for age and sex (OR 1.25, 95% CI 1.14-1.37, p < 0.001) and even after controlling for various other confounding factors including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking, consumption of caffeine or alcohol before sleep, delayed sleep pattern, short sleep duration and habitual snoring (OR 1.20, 95% CI 1.06-1.36, p = 0.003). The findings of our study provide epidemiological evidence that outdoor ALAN is significantly related to obesity.